ArticleBlood2020
Red blood cell microvesicles activate the contact system, leading to factor IX activation via 2 independent pathways.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 89 citations in OpenAlex.
- Lipopolysaccharide and Coagulation Factor XII: Biophysics of Contact Activation in Infection.Seminars in thrombosis and hemostasis · 2026Review
- Potential Role of Contact Pathway Factors in Catheter-Related Thrombosis: Emerging Evidence and Therapeutic Strategies.Biomolecules · 2026Review
- Predicting dialyzer fiber blocking is hard due to high intrapatient variability and limited utility of thrombin generation markers.Scientific reports · 2026Article
- Hemostatic Changes Following Red Blood Cell Transfusion in Critically Ill Patients: A Retrospective Cohort Study.Journal of clinical medicine · 2025Article
- Emerging pathways in thromboinflammation of sickle cell disease: novel findings in disease pathogenesis.Research and practice in thrombosis and haemostasis · 2025Review
- Procoagulant effect of phosphatidylserine-exposed blood cells, endothelial cells and extracellular vesicles in patients with aortic stenosis.Thrombosis journal · 2025Article
- Endothelial dysfunction in patients with type 2 diabetes: the truth is in the blood.The Journal of clinical investigation · 2025Article
- Observational
- Red cell microparticles produced using high-pressure extrusion enhance both primary and secondary hemostasis.Pharmacological reports : PR · 2025Article
- Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes.Neurocritical care · 2025Article
- Adverse effects of microparticles on transfusion of stored red blood cell concentrates.Hematology, transfusion and cell therapy · 2024Article
- Coagulation protease-induced extracellular vesicles: their potential effects on coagulation and inflammation.Journal of thrombosis and haemostasis : JTH · 2024Review
- Factor XII Structure-Function Relationships.Seminars in thrombosis and hemostasis · 2024Review
- Low hemoglobin causes hematoma expansion and poor intracerebral hemorrhage outcomes.bioRxiv : the preprint server for biology · 2024Article
- Plasma kallikrein supports FXII-independent thrombin generation in mouse whole blood.Blood advances · 2024Article
- Admission viscoelastic hemostatic assay parameters predict poor long-term intracerebral hemorrhage outcomes.Research square · 2024Article
- Red Blood Cell Contribution to Thrombosis in Polycythemia Vera and Essential Thrombocythemia.International journal of molecular sciences · 2024Review
- Deciphering mTheranostics · 2024Article
- Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular TrapsInternational journal of biological sciences · 2024Article
- Crucial roles of red blood cells and platelets in whole blood thrombin generation.Blood advances · 2023Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Storage lesion-induced, red cell-derived microvesicles (RBC-MVs) propagate coagulation by supporting the assembly of the prothrombinase complex. It has also been reported that RBC-MVs initiate coagulation via the intrinsic pathway. To elucidate the mechanism(s) of RBC-MV-induced coagulation activation, the ability of storage lesion-induced RBC-MVs to activate each zymogen of the intrinsic pathway was assessed in a buffer system. Simultaneously, the thrombin generation (TG) assay was used to assess their ability to initiate coagulation in plasma. RBC-MVs directly activated factor XII (FXII) or prekallikrein, but not FXI or FIX. RBC-MVs initiated TG in normal pooled plasma and in FXII- or FXI-deficient plasma, but not in FIX-deficient plasma, suggesting an alternate pathway that bypasses both FXII and FXI. Interestingly, RBC-MVs generated FIXa in a prekallikrein-dependent manner. Similarly, purified kallikrein activated FIX in buffer and initiated TG in normal pooled plasma, as well as FXII- or FXI-deficient plasma, but not FIX-deficient plasma. Dual inhibition of FXIIa by corn trypsin inhibitor and kallikrein by soybean trypsin inhibitor was necessary for abolishing RBC-MV-induced TG in normal pooled plasma, whereas kallikrein inhibition alone was sufficient to abolish TG in FXII- or FXI-deficient plasma. Heating RBC-MVs at 60°C for 15 minutes or pretreatment with trypsin abolished TG, suggesting the presence of MV-associated proteins that are essential for contact activation. In summary, RBC-MVs activate both FXII and prekallikrein, leading to FIX activation by 2 independent pathways: the classic FXIIa-FXI-FIX pathway and direct kallikrein activation of FIX. These data suggest novel mechanisms by which RBC transfusion mediates inflammatory and/or thrombotic outcomes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.